The signal transduction pathway in the proliferation of airway smooth muscle cells induced by uroteusin

• Published in: Chinese medical journal Vol. 117; no. 1; pp. 37 - 41
• Main Author: 陈亚红 赵鸣武 姚婉贞 庞永政 唐朝枢
• Format: Journal Article
• Language: English
• Published: 2004
• Subjects: 信号转导途径; 尾加压素; 气道平滑肌细胞; 细胞增殖; 蛋白激酶; 血管收缩剂
• ISSN: 0366-6999; 2542-5641

Background Human urotensin Ⅱ (U Ⅱ ) is the most potent mammalian vasoconstrictor identified so far. Our previous study showed that U Ⅱ is a potent mitogen of airway smooth muscle cells (ASMC) inducing ASMC proliferation in a dose-dependent manner. The signal transduction pathway of U Ⅱ mitogenic effect remains to be clarified. This study was conducted to investigate the signal transduction pathway in the proliferation of ASMC induced by U Ⅱ.Methods In primary cultures of rat ASMCs, activities of protein kinase C (PKC), mitogen-activated protein kinase (MAPK) and calcineurin (CAN) induced by U Ⅱ were measured. The effect of CaN on PKC and MAPK was studied by adding cyclosporin A (CsA), a specific inhibitor of CaN. Using H7 and PD98059, inhibitors of PKC and MAPK, respectively, to study the effect of PKC and MAPK on CaN. The cytosolic free calcium concentration induced by U Ⅱ was measured using Fura-2/AM.Results U Ⅱ 10^-7 mol/L stimulated ASMC PKC and MAPK activities by 44% and 24% (P<0.01), respectively, after incubating for 20 minutes. It increased CaN activity in a time-dependent manner, being 1.68 times as that of control for 24 hours (P<0.01 ). It promoted the cytosolic free calcium concentration increase of 18% (P<0.01). CsA 10^-6 mol/L and H7 50 μmol/L inhibited U Ⅱ-stimulated CaN activity by 45% (P<0.01) and 21%(P<0.05), respectively, while PD98059 50 μmol/L had no effect on CaN activity (P>O.05). CsA 10^-6 mol/L inhibited U Ⅱ-stimulated PKC activity by 14% (P<O.05), while having no effect on MAPK activity (P>O.05). Conclusions U Ⅱ increases cytosolic free calcium concentration and activates PKC, MAPK and CaN. The siclnal transduction pathway between PKC and CaN has cross-talk.